481 GASTRODUODENAL REBLEEDING ON CIMETIDINE
SIR The H2 antagonist cimetidine (and its forerunner metiamide) have been used in the management of haemorrhage from chronic gastroduodenal ulceration,from erosive gastritis in the seriously ill patient.,23 and in association with liver failure.’ We have used intravenous cimetidine (2 mg kg-h"’ for 2 h, repeated 6-hourly) in four seriously ill patients with gastroduodenal hemorrhage, and have failed to arrest ha:morrhage in any of them. All had multiple surgical problems, and in two the precise source of bleeding could not be identified although it was assumed to come from stress ulceration. In that cimetidine is likely to be widely used in an endeavour to avoid operation for bleeding mucosal lesions we think it important to record that in our hands, in complex situations, it appears to be ineffective.
Case1 A 25-year-old soldier was referred with multiple small-bowel nstuts and a high-output gastrojejunal fistula, following a gunshot wound. Parenteral nutrition and fistula management resulted in an improvement but several episodes of gastric hæmorrhage occurred over a 3-week period through the gastrojejunal fistula. Though the fistula output fell, bleeding continued intermittently despite cimetidine for ten days. Bleeding ultimately ceased, but this added to the list of complications which resulted in his death.
Case2 A 70-year-old woman long benign oesophageal
had a jejunal-loop replacement for a stricture unresponsive to dilatation. The cervical anastomosis leaked postoperatively and thereafter the patient had three large melsena stools over a period of a month and required repeated transfusions. Cimetidine therapy was continued throughout. Neither endoscopic nor barium investigations could be performed, but no peptic ulcer had been
demonstrated previously. Case3 A 75-year-old man had a melsena at home and was admitted 3 days later with severe pneumonia. He had been taking steroids for 15 years for chronic bronchitis and emphysema. Cimetidine was not given at this stage. A week later peritonitis developed, and at operation a perforated anterior duodenal ulcer was oversewn. A gastroduodenal fistula developed and then further mebena. Cimetidine was started but over a 10-day period he bled massively on two occasions. At reoperation a bleeding posterior duodenal ulcer was underrun and his fistula closed. He subsequently died from respiratory failure.
gest that it be used with caution and not prescribed if a focal lesion is present and surgery offers prospects of control. H. A. F. DUDLEY Academic Surgical Unit, L. P. FIELDING St. Mary’s Hospital, London W2
G. GLAZER
GASTRIC ULCERATION INDUCED BY SPIRONOLACTONE
SIR--Spironolactone is the principal diuretic in the medical management of ascites,* and its short-term use is largely free from troublesome side-effects. Minor gastrointestinal upsets are well recognised,2 3 but hæmatemesis secondary to gastric ulceration has not previously been demonstrated. We wish to report such a case. A 64-year-old housewife was admitted to hospital in October, 1976, with a 2-month history of nausea, anorexia, increasing abdominal girth, and deepening jaundice. Previous excessive consumption of alcohol was noted. She was considered to have alcoholic cirrhosis with hepatitis and ascites, and was treated with salt and fluid restriction together with incremental doses of spironolactone. 10 days after the start of treatment, while she was receiving spironolactone 600 mg daily in divided doses and no other medication apart from vitamins, she complained of epigastric discomfort and vomited several times. The vomitus on the last occasion consisted of 1 litre of coffee-ground material. Endoscopy within 36 h of this incident demonstrated two round bleeding acute ulcers, 2 cm in diameter, on the greater curvature of the stomach, and no other abnormality in the remainder of the upper gastrointestinal tract. Histology of biopsy samples taken adjacent to the ulcers was normal. A barium meal, carried out one week before the hsematemesis, was normal, and there was no evidence of oesophageal varices. 2 weeks after the haematemesis, following withdrawal of the spironolactone, both ulcers were healed at repeat endoscopy. Greenblatt and Koch-Weser3 reported that in the Boston Collaborative Drug Surveillance Program 2.3% of the patients taking spironolactone had anorexia, nausea, vomiting, and diarrhoea. Epigastric discomfort was less of a problem if the drug was taken with food. However, we can find only one previous report of de-novo gastric ulceration induced by spironolactone,2although exacerbation of pre-existing duodenal ulceration has been noted.4 It is important to recognise gastric ulceration induced by spironolactone as a further cause of upper-gastrointestinaltract bleeding in a clinical condition where haematemesis can have more sinister implications. University Department of Medicine, Infirmary, Glasgow G11 6NT
Western
ALISTAIR MACKAY ROBERT D. STEVENSON
Case4 A 50-year-old man had acute idiopathic pancreatitis which responded well to medical treatment. 11 days after admission he had a large hamatemesis; endoscopy showed a bleeding, shallow lesser-curve ulcer and three other small gastric erosions. Despite continuous cimetidine therapy he had two further large bleeds (3 and 5 days later) which necessitated a Billroth I gastrectomy at which a single subacute ulcer was
found on the lesser curve. Our experience is small and provides a severe test for the drug. Though cimetidine may well have a part to play in the management of acute upper-gastrointestinal bleeding, we sug1
Dykes, P. D., Kang, J. Y., Hoare, A., Hawkins, C. F., Mills, J. G. Second International Symposium on H2 Receptor Antagonists. (In the press.) 2. Burland,W. L., Parr, S. N. ibid 3. MacDonald, A. S., Steele, B. J., Bottomley, M. C. Lancet, 1976, i, 68. 4 Bailey, R. J., MacDougall, B. R. D., Williams, R. Gut, 1976, 17, 389.
TOXIC HEPATITIS AFTER THERAPEUTIC DOSES OF BENORYLATE AND D-PENICELLAMINE of acetylsalicylic acid and parais a valuable drug in the long-term treatment of rheumatoid arthritis. It is considered safe in therapeutic dosage, and children have been given 150-234
SIR,-Benorylate,
cetamol
an ester
(acetaminophen),
in Modern Diuretic Therapy in the Treatment of Cardiovascular and Renal Disease (edited by A. Lant and G. M. Wilson); p. 270. Amsterdam, 1973. 2. Brown, J. J., Ferriss, J. B., Fraser, R., Lever, A. F., Robertson, J. I. S. in Medical Uses of Spironolactone (edited by G. M. Wilson); p. 27. Amsterdam, 1971. 3. Greenblatt, D. J., Koch-Weser, J.J. Am. med. Ass. 1973, 225, 40. 4. Kremer, D., Brown, J. J., Davies, D. L., Fraser, R., Lever, A. F., Robertson, J I. S. Br. med. J. 1973, ii, 216.
1.
Sherlock, S.
SIR The H2 antagonist cimetidine (and its forerunner metiamide) have been used in the management of haemorrhage from chronic gastroduodenal ulceration,from erosive gastritis in the seriously ill patient.,23 and in association with liver failure.’ We have used intravenous cimetidine (2 mg kg-h"’ for 2 h, repeated 6-hourly) in four seriously ill patients with gastroduodenal hemorrhage, and have failed to arrest ha:morrhage in any of them. All had multiple surgical problems, and in two the precise source of bleeding could not be identified although it was assumed to come from stress ulceration. In that cimetidine is likely to be widely used in an endeavour to avoid operation for bleeding mucosal lesions we think it important to record that in our hands, in complex situations, it appears to be ineffective.
Case1 A 25-year-old soldier was referred with multiple small-bowel nstuts and a high-output gastrojejunal fistula, following a gunshot wound. Parenteral nutrition and fistula management resulted in an improvement but several episodes of gastric hæmorrhage occurred over a 3-week period through the gastrojejunal fistula. Though the fistula output fell, bleeding continued intermittently despite cimetidine for ten days. Bleeding ultimately ceased, but this added to the list of complications which resulted in his death.
Case2 A 70-year-old woman long benign oesophageal
had a jejunal-loop replacement for a stricture unresponsive to dilatation. The cervical anastomosis leaked postoperatively and thereafter the patient had three large melsena stools over a period of a month and required repeated transfusions. Cimetidine therapy was continued throughout. Neither endoscopic nor barium investigations could be performed, but no peptic ulcer had been
demonstrated previously. Case3 A 75-year-old man had a melsena at home and was admitted 3 days later with severe pneumonia. He had been taking steroids for 15 years for chronic bronchitis and emphysema. Cimetidine was not given at this stage. A week later peritonitis developed, and at operation a perforated anterior duodenal ulcer was oversewn. A gastroduodenal fistula developed and then further mebena. Cimetidine was started but over a 10-day period he bled massively on two occasions. At reoperation a bleeding posterior duodenal ulcer was underrun and his fistula closed. He subsequently died from respiratory failure.
gest that it be used with caution and not prescribed if a focal lesion is present and surgery offers prospects of control. H. A. F. DUDLEY Academic Surgical Unit, L. P. FIELDING St. Mary’s Hospital, London W2
G. GLAZER
GASTRIC ULCERATION INDUCED BY SPIRONOLACTONE
SIR--Spironolactone is the principal diuretic in the medical management of ascites,* and its short-term use is largely free from troublesome side-effects. Minor gastrointestinal upsets are well recognised,2 3 but hæmatemesis secondary to gastric ulceration has not previously been demonstrated. We wish to report such a case. A 64-year-old housewife was admitted to hospital in October, 1976, with a 2-month history of nausea, anorexia, increasing abdominal girth, and deepening jaundice. Previous excessive consumption of alcohol was noted. She was considered to have alcoholic cirrhosis with hepatitis and ascites, and was treated with salt and fluid restriction together with incremental doses of spironolactone. 10 days after the start of treatment, while she was receiving spironolactone 600 mg daily in divided doses and no other medication apart from vitamins, she complained of epigastric discomfort and vomited several times. The vomitus on the last occasion consisted of 1 litre of coffee-ground material. Endoscopy within 36 h of this incident demonstrated two round bleeding acute ulcers, 2 cm in diameter, on the greater curvature of the stomach, and no other abnormality in the remainder of the upper gastrointestinal tract. Histology of biopsy samples taken adjacent to the ulcers was normal. A barium meal, carried out one week before the hsematemesis, was normal, and there was no evidence of oesophageal varices. 2 weeks after the haematemesis, following withdrawal of the spironolactone, both ulcers were healed at repeat endoscopy. Greenblatt and Koch-Weser3 reported that in the Boston Collaborative Drug Surveillance Program 2.3% of the patients taking spironolactone had anorexia, nausea, vomiting, and diarrhoea. Epigastric discomfort was less of a problem if the drug was taken with food. However, we can find only one previous report of de-novo gastric ulceration induced by spironolactone,2although exacerbation of pre-existing duodenal ulceration has been noted.4 It is important to recognise gastric ulceration induced by spironolactone as a further cause of upper-gastrointestinaltract bleeding in a clinical condition where haematemesis can have more sinister implications. University Department of Medicine, Infirmary, Glasgow G11 6NT
Western
ALISTAIR MACKAY ROBERT D. STEVENSON
Case4 A 50-year-old man had acute idiopathic pancreatitis which responded well to medical treatment. 11 days after admission he had a large hamatemesis; endoscopy showed a bleeding, shallow lesser-curve ulcer and three other small gastric erosions. Despite continuous cimetidine therapy he had two further large bleeds (3 and 5 days later) which necessitated a Billroth I gastrectomy at which a single subacute ulcer was
found on the lesser curve. Our experience is small and provides a severe test for the drug. Though cimetidine may well have a part to play in the management of acute upper-gastrointestinal bleeding, we sug1
Dykes, P. D., Kang, J. Y., Hoare, A., Hawkins, C. F., Mills, J. G. Second International Symposium on H2 Receptor Antagonists. (In the press.) 2. Burland,W. L., Parr, S. N. ibid 3. MacDonald, A. S., Steele, B. J., Bottomley, M. C. Lancet, 1976, i, 68. 4 Bailey, R. J., MacDougall, B. R. D., Williams, R. Gut, 1976, 17, 389.
TOXIC HEPATITIS AFTER THERAPEUTIC DOSES OF BENORYLATE AND D-PENICELLAMINE of acetylsalicylic acid and parais a valuable drug in the long-term treatment of rheumatoid arthritis. It is considered safe in therapeutic dosage, and children have been given 150-234
SIR,-Benorylate,
cetamol
an ester
(acetaminophen),
in Modern Diuretic Therapy in the Treatment of Cardiovascular and Renal Disease (edited by A. Lant and G. M. Wilson); p. 270. Amsterdam, 1973. 2. Brown, J. J., Ferriss, J. B., Fraser, R., Lever, A. F., Robertson, J. I. S. in Medical Uses of Spironolactone (edited by G. M. Wilson); p. 27. Amsterdam, 1971. 3. Greenblatt, D. J., Koch-Weser, J.J. Am. med. Ass. 1973, 225, 40. 4. Kremer, D., Brown, J. J., Davies, D. L., Fraser, R., Lever, A. F., Robertson, J I. S. Br. med. J. 1973, ii, 216.
1.
Sherlock, S.
